No abstract

The role of promoter methylation in the process of cancer cell metastasis has, however, not yet been studied. Recently, methylation of the TPEF (transmembrane protein containing epidermal growth factor and follistatin domain) gene was reported in human colon, gastric, and bladder cancer cells. Using the Methylight assay, TPEF/HPP1 gene methylation was assessed in primary colorectal cancers (n = 47), matched normal colon mucosa, as well as in the liver metastasis of 24 patients with colorectal cancer, and compared to the methylation status of the TIMP-3, APC, DAPK, caveolin-2, and p16 genes. TPEF was frequently methylated in primary colorectal cancers (36 of 47) compared to the normal colon mucosa (1 of 21) (P < .0001), and TPEF mRNA expression in colon cancer cell lines was restored after treatment with 5-aza-2'-deoxycytidine. The p16 and APC genes were also frequently methylated in primary colorectal cancers (P < .02) compared to the normal colon mucosa. Interestingly, promoter methylation was significantly more frequent in proximal, nonrectal cancers (P < .05). Furthermore, a high degree of methylation of the TPEF gene was also observed in liver metastasis (19 of 24). In summary, we observed frequent TPEF methylation in primary colorectal cancers and liver metastases, indicating that epigenetic alterations are not only present in the early phases of carcinogenesis, but are also common in metastatic lesions. The high frequency of TPEF methylation in this series of colorectal cancers underscores the importance of epigenetic changes as targets for the development of molecular tests for cancer diagnosis.

Trauma informed care (TIC) is a whole system organisational change process which emerged from the seminal Adverse Childhood Experiences (ACE) study, establishing a strong graded relationship between the number of childhood adversities experienced and a range of negative outcomes across multiple domains over the life course. To date, there has been no systematic review of organisation-wide implementation initiatives in the child welfare system. As part of a wider cross-system rapid evidence review of the trauma-informed implementation literature using systematic search, screening and review procedures, twenty-one papers reporting on trauma-informed implementation in the child welfare system at state/regional and organisational/agency levels were identified. This paper presents a narrative synthesis of the various implementation strategies and components used across child welfare initiatives, with associated evidence of effectiveness. Training was the TIC implementation component most frequently evaluated with all studies reporting positive impact on staff knowledge, skills and/or confidence. The development of trauma-informed screening processes, and evidence-based treatments/trauma focused services, where evaluated, all produced positive results. Whilst weaknesses in study design often limited generalisability, there was preliminary evidence for the efficacy of trauma-informed approaches in improving the mental and emotional well-being of children served by community-based child welfare services, as well as their potential for reducing caregiver stress and improving placement stability.

Aberrant DNA methylation occurs early in oncogenesis, is stable, and can be assayed in tissues and body fluids. Therefore, genes with aberrant methylation can provide clues for understanding tumor pathways and are attractive candidates for detection of early neoplastic events. Identification of sequences that optimally discriminate cancer from other diseased and healthy tissues is needed to advance both approaches. Using well-characterized specimens, genome-wide methylation techniques were used to identify candidate markers specific for colorectal neoplasia. To further validate 30 of these candidates from genome-wide analysis and 13 literature-derived genes, including genes involved in cancer and others with unknown functions, a high-throughput methylation-specific oligonucleotide microarray was used. The arrays were probed with bisulfite-converted DNA from 89 colorectal adenocarcinomas, 55 colorectal polyps, 31 inflammatory bowel disease, 115 extracolonic cancers, and 67 healthy tissues. The 20 most discriminating markers were highly methylated in colorectal neoplasia (area under the receiver operating characteristic curve > 0.8; P < 0.0001). Normal epithelium and extracolonic cancers revealed significantly lower methylation. Real-time PCR assays developed for 11 markers were tested on an independent set of 149 samples from colorectal adenocarcinomas, other diseases, and healthy tissues. Microarray results could be reproduced for 10 of 11 marker assays, including eight of the most discriminating markers (area under the receiver operating characteristic curve > 0.72; P < 0.009). The markers with high specificity for colorectal cancer have potential as blood-based screening markers whereas markers that are specific for multiple cancers could potentially be used as prognostic indicators, as biomarkers for therapeutic response monitoring or other diagnostic applications, compelling further investigation into their use in clinical testing and overall roles in tumorigenesis. (Mol Cancer Res 2007;5(2):153 -63)

Abstract Social work practice has an essential, yet ambiguous, relationship with theory. This state of affairs is currently evident in the range of contemporary relationship-based practice (RBP) models being applied within Child and Family Social Work. This article argues that there is an urgent need for a theoretically coherent conceptualisation of these models to enable social work practitioners to embrace their common precepts and so enable more effective interventions. In contrast to attempts to show the distinctiveness of current models for reasons of fidelity, model identity and marketing, this unifying approach advocates for recognition of the commonality and complementarity of contemporary RBP models. The article argues that systemic theory which applies a social constructionist orientation can provide this coherence, helping social workers develop their practice in an informed way. In making this case, the emergent evidence base is noted and recommendations are made about how greater convergence and complementarity can be promoted. This article contributes to the debate about how practice and policy should be guided by theoretical ideas of coherence, alongside more utilitarian ideas advocating the importance of evidence and effectiveness.